You couldn’t make body bags fast enough
"On reading," by Simon Wain-Hobson, is a weekly discussion of scientific papers and news articles around gain of function research in virology.
Since January 2024, Dr. Wain-Hobson has written weekly essays for Biosafety Now discussing risky research in virology. You can read his entire series here.
This essay comes with a mental health warning.
The Fouchier and Kawaoka papers on adapting the bird flu H5N1 virus to be efficiently spread between ferrets, and onwards to humans, provoked the dangerous GOF controversy back in 2012. Other papers doing the same thing on H5N1 from China or on different bird flu viruses in the US received much less attention – see end of essay for a list. Among them is the nightmare paper; there is nothing more frightening. It came from a well-known flu research group at the University of Maryland funded by NIH NIAID contract HHSN26620070001.
They took a H7N1 flu virus of ostriches and adapted it to respiratory transmission between ferrets, just as Drs. Fouchier and Kawaoka did with their H5N1 bird flu viruses. Readers will know this is synonymous with human-to-human transmission. Why do this?
Avian H7 influenza viruses are recognized as potential pandemic viruses, as personnel often become infected during poultry outbreaks. H7 infections in humans typically cause mild conjunctivitis; however, the H7N9 outbreak in the spring of 2013 has resulted in severe respiratory disease. To date, no H7 viruses have acquired the ability for sustained transmission among humans. Airborne transmission is considered a requirement for the emergence of pandemic influenza, and advanced knowledge of the molecular changes or signature required for transmission would allow early identification of pandemic vaccine seed stocks, screening and stockpiling of antiviral compounds, and eradication efforts focused on flocks harboring threatening viruses.
The belief that the mutations involved will faithfully reflect those that will show up in nature and the predictive value of this work for public health are all copy pasted from Fouchier & Kawaoka logic.
When inoculated by needle into ferrets, the unadulterated ostrich flu virus killed 3/5 (60%) animals, so a nasty beast like H5N1 bird flu. The surprise was that after ferret respiratory transmission, transmission was not associated with loss of virulence. A surprise in that the ferret adapted bird H5N1 viruses of Fouchier and Kawaoka were less lethal than the initial viruses.
• This novel human flu virus kills as readily as the Ebola virus.
• It’s respiratory transmissible.
• Humans are immunologically naïve to such a virus.
• The recipe is plastered across the cloud, downloadable by any Tom, Dick or Harry curtesy of USG and the proverbial taxpayer.
Gulp. If there was a lab leak or misappropriation of the work the consequences would be… what? We haven’t the slightest idea for nobody would dare extrapolate from ferrets to Sapiens. But what if it remained as virulent, then what? Devastating is too mild a word. COVID-19 or Spanish flu would be peanuts by comparison. Or smallpox - for those who can remember it? The ordinary form is the most common (~90 percent) with a 30 percent case fatality rate. So worse than smallpox which killed around 500 million people in the last 100 years of its existence. Humanized H7N1 flu would be more, in the billion plus range for the first year. You couldn’t make body bags fast enough.
This paper came out at a time when the DGOF research controversy was raging. Sensing sensitivity or vulnerability the paper was accompanied by an editorial from the editor in chief of the Journal of Virology, a vital organ of the American Society for Microbiology (ASM), that published the paper.
Highly pathogenic avian influenza viruses have been sporadically introduced into humans... these strains are more likely more virulent in humans than the 1918 influenza virus A H1N1 pandemic strain... the virulence of this strain in birds suggests that it could be similarly virulent in humans. Emphasis added. No comment needed.
We learn that prior to submission to the Journal of Virology, the University of Maryland Biosafety Committee (representing the host institution where the work was performed) and the NIAID (the funder) studied the issue of whether the work constituted dual-use research of concern. On two counts there was agreement, but they differed on the third, does the knowledge, information, products, technologies meet the definition of DURC. Basically, they disagreed on what constitutes DURC, while neither group recommended against publication. When the work was submitted to the journal, they did not reach a consensus about whether the work represents DURC. Yet they published it even though they couldn’t agree on whether it was DURC, even though these strains are more likely more virulent in humans than the 1918 influenza virus A H1N1 pandemic strain.
No precaution, no putting the issue on hold giving them time to consult more widely. No, no, they pushed the button for publishing a recipe of a virus more dangerous than the smallpox and Ebola viruses. To try and seize a little high ground they reiterate the totally bogus claims that GOF transmission work on these avian viruses may guide preparation of influenza vaccines, and lead to identification of new antiviral drugs. Eight years later we’ve seen nothing. Nada.
You’d be right – nope, just normal - to expect an uproar in the scientific and lay press. Yet there was none. The NIH kept mum. The only person who hollered was this writer. Having complained to the ASM he was asked to write a critique in the ASM journal mBio.
This allowed some elementary, my dear Watson points to be made. Back then not a single human case of H7N1 bird flu virus had been described so where was the public health relevance of the work? Flu viruses mutate and replace each other, just think of seasonal flu for humans. So why perform work on a virus first isolated more than a decade earlier – 2000 to be precise? Totally irrelevant. In the critique readers will spot many themes that crop in the present series of essays.
Not content on writing an editorial accompanying an article describing the genesis of the equivalent of the most terrible biological weapon imaginable, the ASM accompanied On reading’s critique with another editorial entitled The decision to publish an avian H7N1 influenza virus gain-of-function experiment.
Dr. Simon Wain-Hobson has written an opinion piece questioning the decision of the American Society for Microbiology to publish in the Journal of Virology a paper by Sutton et al. that reports mutations in H7N1 influenza virus associated with airborne transmission in ferrets. We, the group of editors constituting an ASM committee that evaluates papers containing potential dual-use research of concern (DURC), provide responses to the three main concerns offered by Dr. Wain-Hobson and explain the rationale underlying the decision to publish this paper.
The stage is set to correct the wayward virologist. Let’s see how they did. Under The underlying science we learn that the original paper was reviewed twice by three senior influenza virologists with ample experience in studies of influenza transmission and pathogenesis. These reviewers concurred that the results were novel, significant, and scientifically sound. Furthermore, the experiments described are consistent with normative and epistemic standards in the field of molecular microbiology currently used for establishing causation.
There is no attempt to enlighten the reader, it’s a case of he said, they said. As the former is outnumbered, he must be wrong. That said, in a conversation eons ago with an editor of the top scientific journal Nature, On reading learnt that they seek out the lone referee that spots the weak point missed by others. So much for smothering tactics.
As the work raised a concern about the possibility of DURC, an additional evaluation of the manuscript was conducted by the ASM DURC Review Committee. This committee obtained opinions from the University of Maryland Institutional Biosafety Committee and the U.S. Department of Health and Human Services. After substantial deliberation, the committee reached consensus to publish the paper.
That’s odd. Remember that earlier quote, did not reach a consensus about whether the work represents DURC. As the sharp Elizabeth Bennet said more than two centuries ago, But in such cases as these, a good memory is unpardonable. This is the last time I shall ever remember it myself (Pride and Prejudice, chapter 59).
Under The internal review process and assessment of DURC we’re served the law and jurisprudence. Evaluation for the possibility of DURC consists of asking three specific questions as specified by the 2012 U.S. Government DURC policy First, does the work involve one of the 15 listed agents and toxins? Second, does the work involve one of the seven specified experiments (or “effects”)? Third, does the resulting knowledge, information, products, or technologies meet the definition of DURC as defined in the policy? For the first the answer is no. The error here from the public health angle is to focus on the starting point of the experiment, not the end point. This anomaly was corrected only in 2024. For the second the answer is yes as per 2004 Fink report. For the third, they prevaricate and say it’s a judgement call while the DURC definition is problematic for journal editors.
In the end they nod it on as others did before them. In this regard, we note that the National Science Advisory Board for Biosecurity [NSABB] recommended unredacted publication of two controversial H5N1 papers in 2012 reporting DURC and that other papers reporting potential DURC have been published since that time. Thus, our decision to publish the Sutton et al. paper is consistent with contemporary practice. We know that the NSABB changed its position with Drs Fauci and Collins present, authors of the erroneous and unprofessional Op Ed entitled A risk worth taking that appeared in the Washington Post (Chilled virology), so this is hardly a rock on which to base a decision. They hide under the establishment umbrella.
This abdication of mental effort shows up once again in the next section Although risk-benefit analyses have value because they foster discussion and can potentially identify important parameters that should be considered, we do not think an accurate (i.e., quantitative) risk-benefit analysis can be performed when neither the risk nor the benefit can be measured in a meaningful way. In our deliberations about the Sutton et al. paper, we relied on the funding agency (NIAID), the U.S. Department of Agriculture, and the University of Maryland Institutional Biosafety Committee to adjudicate biosafety risk. Emphasis added. The words in bold are wonderfully accurate. Then why do people mention risk benefit analyses for such work? As for biosafety risk, they leave it to others even though this H7N1 flu virus experiment dwarfs the results and dangers of the much-discussed Fouchier and Kawaoka experiments. It’s all alone in another league.
Second, the parental A/H7N1 virus is susceptible to oseltamivir and antigenically matched to an A/Netherlands/219/2003 (H7N7) experimental vaccine. Third, all experiments in this study were conducted in an enhanced animal biosafety level 3 laboratory appropriate for highly pathogenic avian influenza virus strains and routinely inspected by both institutional biosafety and United States Department of Agriculture officials. The risk of some type of laboratory accident is not zero, but we think that appropriate steps were taken to diminish risk to a minimum degree. Benefits are similarly difficult to quantify.
• If this virus got out, could you scale up production of oseltamivir and an unapproved vaccine fast enough? Would they be readily available to the entire world? Unlikely.
• Sure, biosafety level three is par for the course, but why do the work given the non-zero risk of a catastrophe? Especially as benefits are similarly difficult to quantify. You can’t conclude, yet you published the work.
In the end, we reached consensus that the potential risks of the study were low (as defined by the appropriate experts) and mitigated further by the experimental strategy used and that there were indeed potential benefits that might lead to improvements in human health.
In the case of publication of the original scientific paper and On reading’s comments, rather than leave the reader to think and formulate their own opinions, they give theirs. This is reminiscent of Terry Pratchitt: The trouble with having an open mind, of course, is that people will insist on coming along and trying to put things in it.
No thoughtful comments are provided in either piece from the ASM. It’s status quo, protecting the establishment. Nothing on the horror of generating of the equivalent of a deadly biological weapon, nothing on the responsibility as publishers that this info might me used by bad actors or rogue states. Note that we’re post 9/11. Nothing on first, do no harm that is incumbent on scientists (Do no harm 1). Nothing on the ethics or morality of this work (Biosomething).
More than a decade, no study has appeared showing that such DGOF studies have moved the field on. To top things off everything is now out of phase with the current Executive Order on DGOF research, and the words of the present NIH Director.
Conclusions
Calamitous. A betrayal of virology, trust in science, thought and the Western intellectual tradition.
Aside 1
The more I see of the world, the more am I dissatisfied with it; and every day confirms my belief of the inconsistency of all human characters, and of the little dependence that can be placed on the appearance of merit or sense.
Elizabeth Bennet, Pride and Prejudice by Jane Austen, 1813.
Aside 2
DGOF experiments on bird flu viruses which have been overshadowed by the Fouchier and Kawaoka papers.
The third DGOF paper on H5N1 bird flu virus is
H7N1 bird flu virus
H7N9 bird flu virus
H9N2 bird flu virus
Aside 3
With the end of the wonderful 2026 Winter Olympics it’s perhaps worth looking at the Olympic Oath:
In the name of the athletes.
In the name of all judges.
In the name of all the coaches and officials.
The athletes’ representative then completes the oath:
We promise to take part in these Olympic Games, respecting and abiding by the rules and in the spirit of fair play, inclusion and equality. Together we stand in solidarity and commit ourselves to sport without doping, without cheating, without any form of discrimination. We do this for the honour of our teams, in respect for the Fundamental Principles of Olympism, and to make the world a better place through sport.
Note mention of the up and down sides in sport. Judges, coaches and officials are drawn in to make the world a better place. Surely that what science is all about, yet science PhDs take no oath. All we have is virtually unknown and toothless 2005 InterAcademy Panel on Biosecurity that no academy promoted, even though it mentioned funders and journals. Even though the down sides could hurt or kill billions. Indescribably sad.
It’s only a matter of time. Published papers only offer a narrow insight - biowarfare agencies or even just a competent rogue virologist have no oversight or regulation. How about weaponising SARS to give it 100% CFR?
https://www.biorxiv.org/content/10.1101/2024.01.03.574008v1.full.pdf
«The recipe is plastered across the cloud, downloadable by any Tom, Dick or Harry curtesy of USG and the proverbial taxpayer.»
Ahem
I don’t k know about Dick or Harry but I for one did not download any virus recipe.